We studied the following three groups (n=6 each): DS on a low (0.3% NaCl) salt diet (LS); DS on a high salt (8% NaCl) diet for 7 weeks (HS); and DS on a high salt diet for 7 weeks, followed by a single 3E9 monoclonal anti-MBG antibody treatment for 5 days (HSAB). Levels of MBG and levels of proteins implicated in pro-fibrotic signaling, and mRNA expression (paired analysis of gene expression, microarray analysis, Qiagen) in left ventricles (LV) and aortae were assessed. In HS vs. LS, BP increased by 74 mmHg (p < 0.01), plasma MBG doubled (p < 0.05), renal MBG excretion increased 6-fold (p < 0.01), tissue weights increased (LV: 2.37 +/- 0.05 vs. 1.62 +/- 0.04 g/kg BW, p < 0.01; aorta: 4.44 +/- 0.17 vs. 3.01 +/- 0.06 mg/mm*kg BW, p < 0.01), and LV collagen rose 3.5-fold. A single intra-peritoneal administration of anti-MBG monoclonal antibody to hypertensive DS (HSAB group) reduces BP by 35 mmHg (p < 0.01) after 5 days, and markedly reduces collagen-1 and weights of left ventricles and aortae (p<0.01) vs. HS group. In hypertensive DS there was a tissue-specific pattern of up-regulation of expression of genes, implicated in TGF-signaling (LV: TGFb1, TGFb2, MAPK3, CTGF, SMADs, collagen-1 (Table 1); aorta: TGFb2, TGFb3, PDGF, fibronectin, SNAIL1, PCOLCE, collagens; Table 2), that was down-regulated following immunoneutralization of MBG. These observations were supported by western blot and qPCR analyses. Thus, immunoneutralization of MBG in DS produces an anti-remodeling effect associated with down-regulation of genes implicated in TGF-induced fibrosis initiated by MBG in salt-sensitive hypertension. ================================================================= Table 1. Paired analysis of gene expression (Z-ratio) in LV of DS: Gene:___HS/LS vs. HSAB/HS:___Gene description: MAPK3___1.64 vs. -2.66___Mitogen activated protein kinase 3 TGFb1___1.72 vs. -2.20___Transforming growth factor beta 1 TGFb2___2.57 vs. -4.27___Transforming growth factor beta 2 CTGF___2.04 vs. -4.90___Connective tissue growth factor Col1a2___0.80 vs. -2.35___Collagen, type 1, alpha 2 ================================================================= Table 2. Paired analysis of gene expression (Z-ratio) in aorta of DS: Gene:___HS/LS vs. HSAB/HS:___Gene description TGFb2___2.46 vs. -1.60___Transforming growth factor beta 2 TGFb3___3.36 vs. -2.13___Transforming growth factor beta 3 PDGFa___1.08 vs. -1.00___Platelet-derived growth factor, alpha polypeptide PDGFra___2.58 vs. -2.43___Platelet-derived growth factor receptor, alpha polypeptide FN______4.75 vs. -4.14___Fibronectin ITG1b____2.14 vs. -2.16___Fibronectin receptor beta 1 SNAI1____2.29 vs. -4.98___Snail 1 homolog PCOLCE___2.55 vs. -2.74___Procollagen C-endopeptidase enhancer Col5a2___2.95 vs. -3.08___Collagen, type 5, alpha 2 Col11a1___1.75 vs. -5.74___Collagen, type 11, alpha 1 Col16a1___2.11 vs. -2.44___Collagen, type 16, alpha 1 Col17a1___1.76 vs. -1.10___Collagen, type 17, alpha 1 Col18a1___2.52 vs. -1.80___Collagen, type 18, alpha 1